Trial Outcomes & Findings for A Study of Tamiflu (Oseltamivir) for Treatment of Influenza With a Focus on (H1N1) 2009 Flu Strain (NCT NCT01032837)

Results Overview

The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

102 participants

Primary outcome timeframe

Day 1 to Day 40

Results posted on

2012-10-02

Participant Flow

Participant milestones

Participant milestones
Measure	Oseltamivir Standard Dose 5 Days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Overall Study STARTED	26	26	25	25
Overall Study Intent-to-Treat	26	26	25	24
Overall Study COMPLETED	26	23	24	22
Overall Study NOT COMPLETED	0	3	1	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Oseltamivir Standard Dose 10 Days Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Overall Study Adverse event/internal illness	1	0	1
Overall Study Withdrew consent	2	0	1
Overall Study Failed to return	0	1	0
Overall Study Refused treatment	0	0	1

Baseline Characteristics

A Study of Tamiflu (Oseltamivir) for Treatment of Influenza With a Focus on (H1N1) 2009 Flu Strain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oseltamivir Standard Dose 5 Days n=26 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=26 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=25 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=24 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.	Total n=101 Participants Total of all reporting groups
Age, Customized 1 to <13 years	7 participants n=5 Participants	7 participants n=7 Participants	7 participants n=5 Participants	6 participants n=4 Participants	27 participants n=21 Participants
Age, Customized 13 to ≤18 years	3 participants n=5 Participants	2 participants n=7 Participants	5 participants n=5 Participants	3 participants n=4 Participants	13 participants n=21 Participants
Age, Customized >18 years	16 participants n=5 Participants	17 participants n=7 Participants	13 participants n=5 Participants	15 participants n=4 Participants	61 participants n=21 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	15 Participants n=7 Participants	14 Participants n=5 Participants	12 Participants n=4 Participants	54 Participants n=21 Participants
Sex: Female, Male Male	13 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	47 Participants n=21 Participants
Race/Ethnicity, Customized Asian	1 participants n=5 Participants	2 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	4 participants n=21 Participants
Race/Ethnicity, Customized Black	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	4 participants n=4 Participants	10 participants n=21 Participants
Race/Ethnicity, Customized White	23 participants n=5 Participants	23 participants n=7 Participants	20 participants n=5 Participants	20 participants n=4 Participants	86 participants n=21 Participants
Race/Ethnicity, Customized White/Black	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	1 participants n=21 Participants

PRIMARY outcome

Timeframe: Day 1 to Day 40

Population: ITT infected (ITTI) Population, including all patients randomized who received at least one dose of study medication with laboratory confirmation of pandemic (H1N1) 2009 influenza infection, excluding patients infected with oseltamivir-resistant influenza A H1N1 H275Y at baseline and patients not shedding virus at baseline.

The time to cessation of viral shedding was measured by viral culture and defined as the time from treatment initiation to the time of the first negative culture with no subsequent positive cultures. Any patient with a positive culture at the last sample time was censored at that time point. Median time to cessation was estimated from the Kaplan-Meier curve.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Time to Cessation of Viral Shedding	65.6 hours Interval 47.5 to 79.9	70.8 hours Interval 62.1 to 101.7	58.1 hours Interval 27.3 to 93.3	74.1 hours Interval 48.6 to 117.5

SECONDARY outcome

Timeframe: Baseline and Days 3, 6, 8, 11, 15 and 40

Population: ITTI

Viral shedding was measured by viral culture from samples obtained from nasal and throat swabs and performed by the central laboratory.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Baseline (n=19, 18, 16, 17)	100 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Day 3 (n=19, 17, 15, 15)	37 percentage of participants	61 percentage of participants	44 percentage of participants	53 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Day 6 (n=19, 17, 15, 15)	0 percentage of participants	0 percentage of participants	6 percentage of participants	12 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Day 8 (n=18, 17, 15, 15)	5 percentage of participants	0 percentage of participants	0 percentage of participants	6 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Day 11 (n=18, 18, 15, 14)	5 percentage of participants	11 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Day 15 (n=18, 14, 15, 12)	0 percentage of participants	0 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Viral Culture Day 40 (n=16, 15, 16, 14)	5 percentage of participants	11 percentage of participants	0 percentage of participants	12 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Days 3, 6, 8, 11, 15 and 40

Population: ITTI

Viral shedding was measured by reverse transcriptase polymerase chain reaction (RT-PCR) from samples obtained from nasal and throat swabs and performed by the central laboratory.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Baseline (n=19, 18, 16, 17)	89 percentage of participants	100 percentage of participants	100 percentage of participants	100 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Day 3 (n=19, 17, 15, 15)	79 percentage of participants	83 percentage of participants	69 percentage of participants	76 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Day 6 (n=19, 17, 16, 15)	26 percentage of participants	28 percentage of participants	50 percentage of participants	47 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Day 8 (n=18, 17, 15, 15)	11 percentage of participants	11 percentage of participants	13 percentage of participants	12 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Day 11 (n=18, 18, 15, 14)	5 percentage of participants	6 percentage of participants	25 percentage of participants	18 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Day 15 (n=18, 14, 15, 12)	0 percentage of participants	6 percentage of participants	0 percentage of participants	6 percentage of participants
Percentage of Participants With Viral Shedding by Clinic Visit as Measured by Reverse Transcriptase Polymerase Chain Reaction Day 40 (n=16, 15, 16, 14)	5 percentage of participants	6 percentage of participants	6 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Days 2 through 15

Population: ITTI

Influenza virus titer measured by viral culture and expressed on a Log10 scale of the 50% Tissue Culture Infective Dose (TCID50; amount of virus required to kill 50% of inoculated tissue culture cells).

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Change From Baseline in Influenza Titer Measured by Viral Culture Baseline (n=19, 18, 16, 17)	3.74 Log10 TCID50 Standard Deviation 1.478	4.06 Log10 TCID50 Standard Deviation 1.235	4.14 Log10 TCID50 Standard Deviation 1.338	4.54 Log10 TCID50 Standard Deviation 0.746
Change From Baseline in Influenza Titer Measured by Viral Culture Day 2 (n=19, 18, 15, 17)	-1.82 Log10 TCID50 Standard Deviation 1.457	-1.17 Log10 TCID50 Standard Deviation 1.138	-1.97 Log10 TCID50 Standard Deviation 1.584	-1.15 Log10 TCID50 Standard Deviation 1.425
Change From Baseline in Influenza Titer Measured by Viral Culture Day 3 (n=19, 18, 15, 17)	-2.38 Log10 TCID50 Standard Deviation 1.670	-2.18 Log10 TCID50 Standard Deviation 1.221	-2.95 Log10 TCID50 Standard Deviation 1.286	-2.88 Log10 TCID50 Standard Deviation 1.296
Change From Baseline in Influenza Titer Measured by Viral Culture Day 4 (n=19, 18, 15, 17)	-3.18 Log10 TCID50 Standard Deviation 1.511	-3.29 Log10 TCID50 Standard Deviation 1.129	-3.33 Log10 TCID50 Standard Deviation 1.368	-3.76 Log10 TCID50 Standard Deviation 0.859
Change From Baseline in Influenza Titer Measured by Viral Culture Day 5 (n=19, 18, 16, 17)	-3.00 Log10 TCID50 Standard Deviation 1.656	-3.43 Log10 TCID50 Standard Deviation 1.140	-3.45 Log10 TCID50 Standard Deviation 1.453	-3.91 Log10 TCID50 Standard Deviation 0.765
Change From Baseline in Influenza Titer Measured by Viral Culture Day 6 (n=19, 18, 15, 17)	-3.22 Log10 TCID50 Standard Deviation 1.488	-3.56 Log10 TCID50 Standard Deviation 1.235	-3.45 Log10 TCID50 Standard Deviation 1.530	-3.99 Log10 TCID50 Standard Deviation 0.726
Change From Baseline in Influenza Titer Measured by Viral Culture Day 7 (n=19, 18, 16, 17)	-3.22 Log10 TCID50 Standard Deviation 1.469	-3.53 Log10 TCID50 Standard Deviation 1.218	-3.58 Log10 TCID50 Standard Deviation 1.331	-4.04 Log10 TCID50 Standard Deviation 0.746
Change From Baseline in Influenza Titer Measured by Viral Culture Day 8 (n=19, 18, 15, 17)	-3.18 Log10 TCID50 Standard Deviation 1.457	-3.56 Log10 TCID50 Standard Deviation 1.235	-3.65 Log10 TCID50 Standard Deviation 1.385	-4.04 Log10 TCID50 Standard Deviation 0.746
Change From Baseline in Influenza Titer Measured by Viral Culture Day 9 (n=19, 18, 14, 16)	-3.24 Log10 TCID50 Standard Deviation 1.478	-3.53 Log10 TCID50 Standard Deviation 1.218	-3.57 Log10 TCID50 Standard Deviation 1.381	-4.08 Log10 TCID50 Standard Deviation 0.688
Change From Baseline in Influenza Titer Measured by Viral Culture Day 10 (n=19, 18, 15, 16)	-3.21 Log10 TCID50 Standard Deviation 1.463	-3.50 Log10 TCID50 Standard Deviation 1.260	-3.55 Log10 TCID50 Standard Deviation 1.334	-4.14 Log10 TCID50 Standard Deviation 0.652
Change From Baseline in Influenza Titer Measured by Viral Culture Day 11 (n=19, 16, 16, 15)	-3.22 Log10 TCID50 Standard Deviation 1.469	-3.42 Log10 TCID50 Standard Deviation 1.524	-3.64 Log10 TCID50 Standard Deviation 1.338	-4.08 Log10 TCID50 Standard Deviation 0.632
Change From Baseline in Influenza Titer Measured by Viral Culture Day 12 (n=19, 18, 15, 15)	-3.11 Log10 TCID50 Standard Deviation 1.669	-3.47 Log10 TCID50 Standard Deviation 1.289	-3.63 Log10 TCID50 Standard Deviation 1.385	-4.10 Log10 TCID50 Standard Deviation 0.653
Change From Baseline in Influenza Titer Measured by Viral Culture Day 13 (n=19, 18, 16, 15)	-3.17 Log10 TCID50 Standard Deviation 1.458	-3.43 Log10 TCID50 Standard Deviation 1.248	-3.64 Log10 TCID50 Standard Deviation 1.338	-4.10 Log10 TCID50 Standard Deviation 0.653
Change From Baseline in Influenza Titer Measured by Viral Culture Day 14 (n=18, 18, 15, 15)	-3.17 Log10 TCID50 Standard Deviation 1.488	-3.56 Log10 TCID50 Standard Deviation 1.235	-3.55 Log10 TCID50 Standard Deviation 1.334	-4.10 Log10 TCID50 Standard Deviation 0.653
Change From Baseline in Influenza Titer Measured by Viral Culture Day 15 (n=18, 17, 14, 15)	-3.14 Log10 TCID50 Standard Deviation 1.456	-3.50 Log10 TCID50 Standard Deviation 1.250	-3.55 Log10 TCID50 Standard Deviation 1.401	-4.10 Log10 TCID50 Standard Deviation 0.653

SECONDARY outcome

Timeframe: 40 days

Population: ITTI Population

The last positive viral isolate from each patient was tested for reduced sensitivity to oseltamivir. Phenotypic assay was performed to determine the susceptibility of the last positive viral isolate from each patient. If required, a genotypic assay to determine the contribution of both the neuraminidase (NA) and hemagglutinin (HA) genes to decreased susceptibility was also performed.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Number of Participants With Development of Oseltamivir-Resistant Influenza Virus	0 participants	1 participants	1 participants	0 participants

SECONDARY outcome

Timeframe: Day 1 through Day 40

Population: ITTI population with fever at Baseline.

Temperature was recorded by the patient in a diary twice daily for 10 days and once daily thereafter. Fever was defined as a body temperature greater than or including 37.8 degrees Celsius (or ≥ 100.04 Fahrenheit). Time to resolution of fever was defined as the total number of hours from the first dose of study medication to the first time at which temperature is ≤ 37.2 degrees Celsius and lasts at least 21.5 hours. Patients who were still febrile at the end of the study period were censored at that time.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=10 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=6 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=8 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=3 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Time to Resolution of Fever	19.3 hours Interval 10.6 to 58.4	35.5 hours Interval 12.7 to 53.1	24.9 hours Interval 15.7 to 45.2	20.0 hours Interval 15.9 to 74.3

SECONDARY outcome

Timeframe: Day 1 to Day 40

Population: ITTI population including children only (ages 1 - 12 years).

Daily influenza-like symptoms (such as poor appetite, irritability, low energy, nasal congestion, runny nose etc) were recorded in a diary on a scale from 0 (no problem) to 3 (major problem). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'no problem' or 'minor problem' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=6 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=4 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=4 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=3 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Time to Alleviation of All Clinical Symptoms - Children	176.8 hours Interval 67.5 to 302.0	127.7 hours Interval 32.6 to 281.8	118.8 hours Interval 46.3 to 228.2	123.1 hours Interval 7.1 to 232.3

SECONDARY outcome

Timeframe: Day 1 to Day 40

Population: ITTI population including adults only (\>12 years old).

Daily influenza-like symptoms (such as nasal congestion, sore throat, cough, aches and pains, fatigue, headache, chills) were recorded in a diary on a scale from 0 (absent) to 3 (severe). A patient is considered free of all clinical influenza symptoms if all symptoms were checked as 'absent' or 'mild' (i.e., symptom score ≤1). Time to alleviation of all clinical symptoms was defined as the number of hours from the first dose to the first time the patient had alleviation of all symptoms. Patients without alleviation of symptoms were censored at the last available assessment.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=13 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=14 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=12 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=14 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Time to Alleviation of All Clinical Symptoms - Adults	140.0 hours Interval 99.8 to 183.1	181.8 hours Interval 87.0 to 354.6	146.8 hours Interval 109.1 to 237.8	94.9 hours Interval 57.2 to 261.2

SECONDARY outcome

Timeframe: Day 1 through Day 40

Population: ITTI population

The number of participants who developed secondary illnesses due to influenza, including four pre-defined adverse events: otitis media, bronchitis, pneumonia, or sinusitis at any time during the study.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Number of Participants Who Developed Secondary Illnesses During the Study Bronchitis	1 participants	0 participants	0 participants	0 participants
Number of Participants Who Developed Secondary Illnesses During the Study Otitis media	0 participants	0 participants	0 participants	0 participants
Number of Participants Who Developed Secondary Illnesses During the Study Pneumonia	0 participants	0 participants	0 participants	0 participants
Number of Participants Who Developed Secondary Illnesses During the Study Sinusitis	0 participants	0 participants	0 participants	2 participants
Number of Participants Who Developed Secondary Illnesses During the Study Any secondary illness	1 participants	0 participants	0 participants	2 participants

SECONDARY outcome

Timeframe: Day 1 through Day 40

Population: ITTI population

The number of participants who developed secondary illnesses due to influenza, including otitis media, bronchitis, pneumonia, or sinusitis at any time during the study which were treated with antibiotics.

Outcome measures

Outcome measures
Measure	Oseltamivir Standard Dose 5 Days n=19 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=18 Participants Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=16 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=17 Participants Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Number of Participants Who Developed Secondary Illnesses That Were Treated With Antibiotics	0 participants	0 participants	0 participants	2 participants

Adverse Events

Oseltamivir Standard Dose 5 Days

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Oseltamivir Standard Dose 10 Days

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Oseltamivir High Dose 5 Days

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Oseltamivir High Dose 10 Days

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Oseltamivir Standard Dose 5 Days n=26 participants at risk Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir Standard Dose 10 Days n=26 participants at risk Adults and children 13 years and older received 75 mg oseltamivir and a placebo capsule twice daily for 10 days. Children aged 1 - 12 years received a weight-based dose (from 30 to 75 mg) oseltamivir suspension and placebo suspension orally twice daily for 10 days.	Oseltamivir High Dose 5 Days n=25 participants at risk Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 5 days. Children aged 1 - 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 5 days. Participants received matching placebo for the second 5 days of treatment.	Oseltamivir High Dose 10 Days n=24 participants at risk Adults and children 13 years and older received 150 mg (2 x 75 mg) oseltamivir capsules twice daily for 10 days. Children aged 1- 12 years received a weight-based dose (from 60 to 150 mg) oseltamivir suspension orally twice daily for 10 days.
Gastrointestinal disorders Vomiting	0.00% 0/26	7.7% 2/26	0.00% 0/25	25.0% 6/24
Gastrointestinal disorders Nausea	3.8% 1/26	3.8% 1/26	4.0% 1/25	8.3% 2/24
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/26	0.00% 0/26	8.0% 2/25	8.3% 2/24
Infections and infestations Upper respiratory tract infection	3.8% 1/26	7.7% 2/26	0.00% 0/25	0.00% 0/24
Musculoskeletal and connective tissue disorders Back pain	7.7% 2/26	0.00% 0/26	0.00% 0/25	0.00% 0/24

Additional Information

Medical Communications

Hoffman-LaRoche

Phone: 800-821-8590

Results disclosure agreements

Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER